Although certain 9-cyclohexylpurines exhibit biological activity, antiviral ring-expanded carbocyclic nucleoside analogs have not been reported. The antiviral activity of cyclobutane derivatives (cyclobut-A,G) suggests ring- size as an important variable. To examine this hypothesis, 6-membered unsaturated nucleoside analogs will be stereo-specifically synthesized and evaluated for antiviral activity. These compounds are homologs of carbovir, a promising carbocyclic anti-HIV agent. Cis and trans 4- hydroxymethyl and 4-hydroxy derivatives will be prepared to assess N1-OH spacing, conformation and 1o vs 2o hydroxyl functionality. Four bases will be used: guanine, adenine, 2-amino-6-chloropurine and thymine. Saturated and unsaturated 3-substituted ring-expanded carbocyclics will also be synthesized. The stereospecific methods employed should be generally useful for nucleoside synthesis. Thus nucleophilic ring-opening of 1,2- anhydro sugars will be examined, and novel isonucleosides will be obtained from available epoxides. Enzymatic kinetic resolution techniques will be applied to racemic products to develop practical general procedures for the preparation of enantiomerically pure nucleoside analogs. New products will be screened for antiviral activity.